Homemade Harmine+GLP-1 Combos

So we know the synergy harmine and GLP-1 exhibit on beta cell specific regeneration. The research done in the lab of Dr. Andrew Stewart (and published in Science of Translational Medicine) has found that the deactivation of a particular brake system in beta cells by the plant compound harmine when combined with the known activating principles of beta cell signaling of GLP-1 leads to marked increases in beta cell specific regeneration. It's all a wordy way of saying "when you take harmine and a GLP-1 promoting compound beta cells benefit".

There has since been a follow up paper looking into the exact mechanisms of how this beta cell regeneration occurs. Karakose et al (2024) found that this unique blend of compounds channeled a previously unrecognized chain of development to direct both new cells and old cells to divert to beta cells. It was a remarkable demonstration of how adaptable the body is given the right circumstances.

And it seems that harmine and GLP-1 are some special ingredients in creating those circumstances.

In the context of the research, harmine and the GLP-1 promoting compounds can seem far-off. Where is this harmine being sourced from? What GLP-1 medication is the "right" one? How do we make this potent combo more accessible?

🧪 Goal-Oriented Synergy: Harmine + GLP-1 Production

🧬 Harmine’s Role

Harmine is a DYRK1A inhibitor, which allows for β-cell proliferation—but this growth must be mature, glucose-responsive, and contextually supported by gut-liver immune coordination. So we need to pair it with compounds that:

• Encourage GLP-1 secretion

• Support intestinal L-cell function

• Reduce inflammatory load

• Ensure the new β-cells are functional, not dysfunctional clones

Harmine is a naturally occuring plant compound found across several different plant species.

Among them:

• Syrian rue (Peganum harmala)

• Ayahuasca vine (Banisteriopsis caapi)

• Passionflower (Passiflora incarnata)

• Tobacco (Nicotiana rustica).

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To maximize the synergy between harmine (from Syrian Rue) and GLP-1 elevation—especially with our goal of beta cell regeneration and metabolic restoration—you want to layer in compounds that do three things:

1. Stimulate endogenous GLP-1 production from L-cells (primarily in the gut)

2. Prolong GLP-1 activity by inhibiting its degradation (especially by DPP-4)

3. Create a receptive terrain—repairing gut, liver, and immune tone—so that the GLP-1 signal is both produced and received

💊 GLP-1’s Role

GLP-1, or Glucagon Like Peptide 1, is an endogenous peptide secreted in the L-cells of the intestinal tract. It is responsible for influencing and coordinating things like appetite, insulin release, insulin sensitivity and speed of digestion. GLP-1 is the base molecule from which commercial variations like Ozempic, Wegovy, Trulicity etc. are centered around.

While all of this sounds cool. Plant compounds that work together to make more beta cells? Sign me up. But where the science leads us in theory, it falls short in practicality. What do we do with this information?

Those with autoimmune conditions almost always have compromised gut integrity. Damaged gut walls meals faulty L-cells. No L-cells, no GLP-1. So those with type 1 diabetes want both GLP-1 AND the ability to make their own.

Let's see if we can come up with some alternative methods

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In the realm of harmine, Syrian rue has been the most accessible and potent source. Powderized and encapsulated rue seeds seems like an intuitive way to get harmine into our system. It avoids any of the alcohol extraction methods that are more labor intensive and have a greater margin for error (and, in my opinion, tastes horrible). Capsules have been my go-to way for harmine consumption ever since I learned about it 3 years ago. I buy whole seeds, ground them up and encapsulate them myself using a special capsule-making contraption (linked here)

When it comes to GLP-1, things get a little more complex. Here's why:

1. Are there a thousand companies right now ready to sell you a month's supply of GLP-1? Yes.

2. Does injecting this compound into our body do anything to support our natural production? No. Or address the deficits that caused us to lose it in the first place? Nope.

3. What about rebuilding the terrain of our gut to help it better produce its own GLP-1? No.

4. Does sourcing GLP-1 without healing the system meant to provide it create a stable foundation for LASTING results? Remember, we don't want a band-aid. We want self-sustaining systems. Again, no.

So the "straight to GLP-1" route may not be ideal for the long run. This requires us to consider how we can improve our gut health to the point where its generating its own GLP-1. How do we do that?

There are levels to gut health, right? Microbial diversity, mucus membranes, intestinal wall integrity. Behind these levels are even more variables: dietary intake, liver health, nutrient stores, vitamin and mineral balance.

What are the natural sources of balance each level of gut health, both individually and systemically, need in order to thrive again?

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🔹 Layer 1: GLP-1 Secretagogues

Support L-cells and their secretion of GLP-1, critical for β-cell support and insulin regulation.

Because of GLP-1's inhibitory effect on alpha cell expression, combining it with harmine funnels its regenerative capacity to beta cells.

Compound	Role	Note
Dandelion root	Bile support, mild bitter	Improves digestion and may stimulate L-cell activation via bitter receptors
Gentian root	Potent bitter	Strong activator of bitter taste receptors on enteroendocrine cells
Psyllium husk	Soluble fiber	Promotes SCFA production (esp. butyrate, which stimulates GLP-1)
Inulin	Prebiotic fiber	Feeds bifidobacteria, supports butyrate and GLP-1 pathways
Aloe vera	Gut-soothing + mucosal repair	Enhances gut integrity, may support L-cell niche stability

🔹 Layer 2: Mucosal & Barrier Restoration

Ensure intestinal integrity so L-cells function properly and systemic inflammation is minimized.

Compound	Role	Note
Marshmallow root	Mucilage-rich, gut coating	Calms inflammation, protects gut lining
Slippery elm bark	Mucosal support + fiber	Encourages microbial balance and barrier repair
Licorice root	Mucosal repair + cortisol regulation	Supports adrenal-liver-gut axis
Cinnamon	Blood sugar modulation + microbiota support	Enhances insulin sensitivity and digestion

🔹 Layer 3: Liver & Inflammatory Control

Support the liver’s role in GLP-1 clearance, bile flow, and immune tolerance.

Compound	Role	Note
Beet root powder	Liver phase 2 detox & nitric oxide	Enhances methylation and microcirculation
Turmeric	Anti-inflammatory & bile support	Synergizes with fiber for microbiome modulation
Clove	Anti-parasitic + warming	Reduces pathogenic burden, supports digestion
Coriander/Cumin	Carminative & digestive aid	Reduces bloating, supports microbial harmony

When I first took to this approach, I had accrued a collection of different herbs. Cinnamon and turmeric for blood sugar balance. Licorice and dandelion for liver and digestion support. Being that I've been at this for several years, I have a stash in my cabinets.

I also have a grain mill that I use to make homemade flour, so why couldn't it make powders of some of my herbs, roots and barks? Let's take what I have in my cabinets and see if we can build an ideal harmine+GLP-1 blend.

My Stash (*sourced mainly from Mountain Rose Herbs):

• Syrian Rue seeds

• *Dandelion Root

• *Licorice Root

• *Marshmallow Root

• *Gentian Root

• *Cacao Powder

• *Cinnamon

• *Slipper Elm Bark

• *Aloe Vera Powder

• *Psyllium husk

• Inulin powder

• Turmeric Powder

• Clove Powder

💡 Foundational Herbal Pairing Strategy

🔹 Base: Syrian Rue (Harmine source)

• Contains harmine, harmaline, and tetrahydroharmine

• Potent DYRK1A inhibitor → stimulates β-cell replication

Here is what I've followed into terms of dosing: The amount of harmine in Syrian rue seeds varies based on the seed quality, region, and preparation, but on average, Syrian rue seeds contain 2–7% harmala alkaloids, with harmine comprising about 50–70% of the total alkaloids.

Estimated Harmine Content:

1. If 2 size 00 capsules contain ~1.2–1.4 grams of Syrian rue powder:

   • Harmala alkaloid content: 2–7% of 1.2–1.4 g = 24–98 mg of harmala alkaloids.

   • Harmine content (50–70% of alkaloids): 12–68 mg of harmine.

Summary:

• In 2 size 00 capsules (1.2–1.4 g of powder), you can expect 12–68 mg of harmine. The variability depends on the seed's alkaloid concentration.

For precise dosing, lab testing or using purified extracts is recommended. But I operate under the assumption that two size 00 capsules is giving me atleast the minimum effective dose of harmine.

🔹 Bonus: β-cell Microenvironment Support

• Cacao powder: Contains flavonoids that protect β-cells and boost insulin sensitivity

• Cinnamon: Improves insulin receptor signaling, supports antioxidant status

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🔥 Strongest Natural Pro-GLP-1 Compounds to Pair with Harmine

Here is an expanded list of natural products with a known connection to GLP-1 promotion.

Compound / Extract	Mechanism	Bonus Support
Berberine (from Coptis, Barberry)	Increases GLP-1 secretion; improves insulin sensitivity; inhibits DPP-4	Antimicrobial, liver support, gut healing
Ginger (especially 6-Gingerol)	Stimulates GLP-1 from gut; improves gastric motility (amylin synergy)	Gut-liver synergy, anti-inflammatory
Cinnamon (Ceylon ideal)	Enhances GLP-1 release and insulin signaling	Reduces postprandial glucose
Curcumin	Boosts GLP-1 via gut microbiome and bile acid modulation	Liver repair, bile flow, microbiome resilience
Resveratrol	Enhances GLP-1 secretion and receptor sensitivity	SIRT1 activation, anti-aging, metabolic benefit
Inulin (prebiotic fiber)	Increases butyrate → stimulates L-cell GLP-1 production	Microbiome support, gut lining repair
Butyrate (sodium butyrate or from diet)	Directly stimulates GLP-1 production from colonocytes	Gut integrity, immune modulation
Green Tea Extract (EGCG)	Mild DPP-4 inhibitor, improves L-cell output	Anti-inflammatory, glucose stabilization
Mulberry Leaf Extract	Enhances GLP-1; inhibits intestinal glucose absorption	Blood sugar control, beta cell protection
Bitter Melon	GLP-1 secretion stimulator via gut stimulation	Pancreatic islet and insulin regulation support
Aloe Vera Powder	Enhances L-cell recovery and mucosal signaling	Gut healing, L-cell membrane support
Gentian Root / Bitters	Stimulates bitter receptors → enteroendocrine activation	Improves bile, digestion, liver signal cascades

🧠 Key Combination Strategies

1. Harmine + Berberine + Ginger + Cinnamon

• Berberine amplifies GLP-1 and mimics metformin in gut-liver axis

• Ginger & cinnamon activate gut motility and insulin co-secretion

• Harmonizes glucose, beta cell, and gut signals

2. Harmine + Butyrate Enhancers (Inulin, Aloe, Slippery Elm)

• Builds the terrain for L-cell repair

• Enhances native GLP-1 in colon and ileum

• Supports mucosal immunity and local signaling

3. Harmine + Bitter Stimulators (Gentian, Dandelion, Coptis)

• Activates the upper gut cascade (bile, GLP-1, CCK, etc.)

• Supports detox and enteroendocrine readiness

4. Harmine + Mulberry + Green Tea Extract

• Dual GLP-1 support with blood sugar and DPP-4 inhibition

• Antioxidant-rich, vascular support, and Treg-friendly

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🧬 Notes on Synergy with Harmine

• Harmine inhibits DYRK1A, promoting β-cell proliferation and neuroendocrine plasticity, but the success of this action depends on terrain readiness.

  • That's to say, its worth investing in rebuilding your gut terrain (and addressing exisitng inflammation) BEFORE jumping right into harmine use

• GLP-1 is a critical co-factor that encourages β-cell maturation and survival, making simultaneous elevation an ideal pairing.

• You want a steady-state GLP-1 signal, not spikes, so stacking slow-digesting GLP-1 activators (fiber, bitters, adaptogens) is ideal.

I made the mistake of going straight to harmine when I first learned of it. While I did experience initial decreases in insulin needs, the progress eventually plateaued. This was because I had not laid the appropriate groundwork to sustain that beta cell growth. After a few months I made the switch to improving my gut, liver and nervous system terrain as the top priority. I have since reintroduced Syrian rue powder in small installments to test for blood sugar responses. Each new round comes with its own signs of improvement. Thus far signs of inflammation and terrain instability persist so I continue cycling rebuilding with harmine use.

This very article resulted from some of my brainstorming on new ways to maximize the potential and timeliness of beta cell regrowth.

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🍵 Other Powder Combo Ideas

You could create two synergistic blends:

1. Gut-GLP-1 Synergy Blend

• Inulin

• Psyllium husk

• Aloe vera powder

• Dandelion root

• Gentian root

• Marshmallow root

• Slippery elm bark

💡 Take before meals to prep L-cells, soothe mucosa, and support bile flow.

2. Harmine + Liver Support Combo

• Syrian rue (low dose, e.g., 250–500 mg)

• Licorice root

• Beet root powder

• Cinnamon

• Cacao

• Turmeric (with black pepper)

💡 Take away from high-fiber blends to avoid interference with absorption. Best on an empty stomach or mid-morning.

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📅 Dosing Strategy

• Morning: GLP-1 precursors (ginger, cinnamon, green tea, bitters) + harmine

• Midday: Fiber + prebiotics (inulin, aloe, marshmallow) to feed butyrate

• Evening: Calming gut-liver repair herbs (licorice, slippery elm, aloe)

• Optional: Butyrate (oral or via food) around largest meal to mimic GLP-1 release

Remember that all of this is exploratory. There is no "right" way to do this. Do your due diligence to decide what suits your circumstances. Take small, consistent actions. Look for feedback from your body: Digestion, energy, blood sugars etc. and make changes accordingly.

It could start as a tea blend in the morning. It could be capsules grouped with meals. Powders mixed directly into meals. Perhaps a combination of all three. Get curious and start exploring!

⚠️ Safety Notes

• Syrian rue is MAOI-active: Do not combine with tyramine-rich foods, SSRIs, or stimulant herbs.

• Licorice root can raise blood pressure if taken long-term in high doses.

• Start small: Introduce one blend at a time to gauge tolerance.

Here are some of the links for companies I use to source my materials: Mountain Rose Herbs Syrian Rue